Gram negative bacteria are the causative agents for a number of human pathologies and there is a need for effective vaccines to be developed against many of these bacteria. There is accordingly a need to identify further antigens, such as outer membrane proteins, which are well conserved within, and possibly between, Gram-negative species in order that such antigens may be useful as vaccine components.
In the case of serogroup B of N. meningitidis, the development of a vaccine has been impeded due to the fact that the polysaccharide capsule is poorly immunogenic owing to its immunologic similarity to human polysialylated glycoproteins such as neural cell adhesion molecule. Strategies for vaccine production have therefore concentrated on the surface exposed structures of the meningococcal outer membrane such as PorA, but have been hampered by the high antigenic variability of the major outer membrane proteins among strains.
However, N. meningitidis has recently been found to express an outer membrane protein, “TdfI” or “ZnuD” (BASB082 of WO 00/55327; locus tag NMB0964 in the sequenced genome of N. meningitidis serogroup B; herein SEQ ID NO. 1) involved in the uptake of extracellular zinc. This is surprising as it was previously believed that zinc crosses the outer membrane by passive diffusion through porins, and this finding is the first discovery of a protein involved in zinc uptake across the outer membrane of a Gram-negative bacterium.